Project Summary/Abstract Approximately 114 million surgical and procedure-based wounds occur annually worldwide, including 36 million from surgery in the U.S. Damages to delicate soft tissues, such as lung, liver, land blood vessels, are particularly challenging to repair. When these tissues are punched for biopsy or injured during procedures, they must be reconnected surgically using sutures, staples, or implantation of surgical meshes. Despite their common use in clinics, these mechanical methods are associated with inevitable tissue damages caused by deep piercing and ischemia. These methods are also time-consuming, demand surgeon's skills during the surgeries, and might cause post-surgical complications such as infection. To resolve these issues, various types of surgical materials have been used for sealing, reconnecting tissues, or attaching devices to tissues. Despite the emergence of several surgical sealants, the biomaterials used as sealants/adhesives often have some drawbacks that limit their applications, such as low mechanical properties, toxicity effects or toxic degradation products, and poor adhesive strength; therefore none of them meet all the necessary needs to replace sutures and staples. An ideal surgical sealant is required to be flexible to be able to adapt with dynamic movement of native tissues, have excellent biocompatibility and controlled biodegradability, and provide high adhesive strength and burst pressure particularly in the presence of body fluids. In this proposal, we aim to engineer a novel and highly adhesive surgical sealant with tunable adhesion strength from a light-activated naturally derived hydrogel, gelatin methacryloyl (GelMA), for surgical applications (e.g. lung surgery). We will chemically modify the engineered GelMA hydrogels with catechol to form gelatin methacryloyl-catechol (GelMAC) with enhanced adhesion to the native tissues. We will then evaluate the function of the engineered surgical material as a lung sealant in both small and large animal models. Our preliminary data suggests that this material is superior to the existing products in the market and may generate a paradigm-shifting surgical material that may not require sutures due to its superior mechanical and adhesive properties. The engineered highly adhesive surgical sealant can be potentially used to stop air leakages after lung surgery and also support new tissue formation to repair the defected sites. Due to its high adhesion to the native tissues and biocompatibility, the engineered adhesives in this proposal have potential to be used in various procedures such as anastomoses, cardiovascular surgeries, and wound closure.